Differential Gene Expression and Clonal Selection during Cellular Transformation Induced by Adhesion Deprivation
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE24893 | GEO | 2010/11/14
SECONDARY ACCESSION(S): PRJNA132191
REPOSITORIES: GEO
Similar Datasets
Project description:BackgroundAnchorage independent growth is an important hallmark of oncogenic transformation. Previous studies have shown that when adhesion dependent fibroblasts were prevented from adhering to a substrate they underwent anoikis. In the present study we have demonstrated how anoikis resistant cells gain the transformation related properties with sequential selection of genes. We have proposed this process as a model system for selection of transformed cells from normal cells.ResultsThis report demonstrates that some fibroblasts can survive during late stages of anoikis, at which time they exhibit transformation-associated properties such as in vitro colony formation in soft agar and in vivo subcutaneous tumour formation in nude mice. Cytogenetic characterisation of these cells revealed that they contained a t (2; 2) derivative chromosome and they have a selective survival advantage in non adherent conditions. Gene expression profile indicated that these cells over expressed genes related to hypoxia, glycolysis and tumor suppression/metastasis which could be helpful in their retaining a transformed phenotype.ConclusionOur results reveal some new links between anoikis and cell transformation and they provide a reproducible model system which can potentially be useful to study multistage cancer and to identify new targets for drug development.
| S-EPMC3012028 | biostudies-literature
Project description:This SuperSeries is composed of the following subset Series: GSE24877: Differential Gene Expression and Clonal Selection during Cellular Transformation Induced by Adhesion Deprivation (A16 vs NA16) GSE24878: Differential Gene Expression and Clonal Selection during Cellular Transformation Induced by Adhesion Deprivation (A16 vs COLONY) GSE24879: Differential Gene Expression and Clonal Selection during Cellular Transformation Induced by Adhesion Deprivation (A16 vs. Tumor) Refer to individual Series
2010-11-14 | E-GEOD-24893 | biostudies-arrayexpress
Project description:Cell substrate adhesion plays an important role in cellular transformation of rat fibroblast cell lines, however a few viable non-adherent fibroblast cells when placed in suspension for a time period of 16 h (NA16) showed varied phenotypic characteristics like colony and tumor formation In order to understand the molecular events associated with adhesion independent cell survival ability of NA16, whole genome profiling was performed using Affymetrix Rat 230_2 GeneChips Keywords: Expression profiling of a adhesion deprived transformed cell line F111 fibroblast cell lines were grown in adhesion (A16) and suspension (NA16) conditions for 16h. These suspension cells (NA16) were plated on soft agar for colony formation and also injected in nude mice subcutaneously for tumor formation. A16 samples were considered as the control ones. Total RNA isolated from the samples (A16, NA16, Colony and Tumor) was subjected for expression analysis using Affymetrix Rat 230.2 GeneChip System. The experiment was repeated biologically and technically twice.
2010-11-14 | E-GEOD-24877 | biostudies-arrayexpress
Project description:Cell substrate adhesion plays an important role in cellular transformation of rat fibroblast cell lines, however a few viable non-adherent fibroblast cells when placed in suspension for a time period of 16 h (NA16) showed varied phenotypic characteristics like colony and tumor formation In order to understand the molecular events associated with adhesion independent cell survival ability of NA16, whole genome profiling was performed using Affymetrix Rat 230_2 GeneChips Keywords: Expression profiling of a adhesion deprived transformed cell line F111 fibroblast cell lines were grown in adhesion (A16) and suspension (NA16) conditions for 16h. These suspension cells (NA16) were plated on soft agar for colony formation and also injected in nude mice subcutaneously for tumor formation. A16 samples were considered as the control ones. Total RNA isolated from the samples (A16, NA16, Colony and Tumor) was subjected for expression analysis using Affymetrix Rat 230.2 GeneChip System. The experiment was repeated biologically and technically twice.
2010-11-14 | E-GEOD-24878 | biostudies-arrayexpress
Project description:Cell substrate adhesion plays an important role in cellular transformation of rat fibroblast cell lines, however a few viable non-adherent fibroblast cells when placed in suspension for a time period of 16 h (NA16) showed varied phenotypic characteristics like colony and tumor formation In order to understand the molecular events associated with adhesion independent cell survival ability of NA16, whole genome profiling was performed using Affymetrix Rat 230_2 GeneChips Keywords: Expression profiling of a adhesion deprived transformed cell line F111 fibroblast cell lines were grown in adhesion (A16) and suspension (NA16) conditions for 16h. These suspension cells (NA16) were plated on soft agar for colony formation and also injected in nude mice subcutaneously for tumor formation. A16 samples were considered as the control ones. Total RNA isolated from the samples (A16, NA16, Colony and Tumor) was subjected for expression analysis using Affymetrix Rat 230.2 GeneChip System. The experiment was repeated biologically and technically twice.
2010-11-14 | E-GEOD-24879 | biostudies-arrayexpress
Project description:Cell substrate adhesion plays an important role in cellular transformation of rat fibroblast cell lines, however a few viable non-adherent fibroblast cells when placed in suspension for a time period of 16 h (NA16) showed varied phenotypic characteristics like colony and tumor formation In order to understand the molecular events associated with adhesion independent cell survival ability of NA16, whole genome profiling was performed using Affymetrix Rat 230_2 GeneChips Keywords: Expression profiling of a adhesion deprived transformed cell line
2010-11-14 | GSE24877 | GEO
Project description:Cell substrate adhesion plays an important role in cellular transformation of rat fibroblast cell lines, however a few viable non-adherent fibroblast cells when placed in suspension for a time period of 16 h (NA16) showed varied phenotypic characteristics like colony and tumor formation In order to understand the molecular events associated with adhesion independent cell survival ability of NA16, whole genome profiling was performed using Affymetrix Rat 230_2 GeneChips Keywords: Expression profiling of a adhesion deprived transformed cell line
2010-11-14 | GSE24879 | GEO
Project description:Cell substrate adhesion plays an important role in cellular transformation of rat fibroblast cell lines, however a few viable non-adherent fibroblast cells when placed in suspension for a time period of 16 h (NA16) showed varied phenotypic characteristics like colony and tumor formation In order to understand the molecular events associated with adhesion independent cell survival ability of NA16, whole genome profiling was performed using Affymetrix Rat 230_2 GeneChips Keywords: Expression profiling of a adhesion deprived transformed cell line
2010-11-14 | GSE24878 | GEO
Project description:Cancer cells consistently exhibit decreased stiffness; however, the onset and progression of this change have not been characterized. To study the development of cell stiffness changes, we evaluated the shear stiffness of populations of cells during transformation to a carcinogenic state. Bronchial epithelial cells were exposed to sodium arsenite to initiate early stages of transformation. Exposed cells were cultured in soft agar to further transformation and select for clonal populations exhibiting anchorage-independent growth. Shear stiffness of various cell populations in G1 was assessed using a novel non-invasive assay that applies shear stress with fluid flow and evaluates nanoscale deformation using quantitative phase imaging (QPI). Arsenic-treated cells exhibited reduced stiffness relative to control cells, while arsenic clonal lines, selected by growth in soft agar, were found to have reduced stiffness relative to control clonal lines, which were cultured in soft agar but did not receive arsenic treatment. The relative standard deviation (RSD) of the stiffness of Arsenic clones was reduced compared with control clones, as well as to the arsenic-exposed cell population. Cell stiffness at the population level exhibits potential to be a novel and sensitive framework for identifying the development of cancerous cells.
| S-EPMC5862275 | biostudies-literature
Project description:IntroductionTyrosine phosphorylated signal transducer and activator of transcription 3 (pStat3) is present in numerous cancers and is required for mediating tumorigenesis. Autocrine and paracrine interleukin (IL)-6 signaling is the principal mechanism by which Stat3 is persistently phosphorylated in epithelial tumors including breast, lung, colon and gastric cancer. The Ras oncogene mediates cellular transformation without evidence of pStat3 in cultured cells. Recently, however non-tyrosine phosphorylated Stat3 was shown to have a transcriptional activating function, a role in mitochondrial function and to mediate cell migration.. Here we examined the role of Stat3 in Ras mediated transformation.MethodsHa-rasV12 transformed mammary epithelial cells (MCF10A) cells were transduced with a Stat3shRNA, IL-6shRNA and/or treated with inhibitors of Janus kinases (JAKs) to examine the role of the IL-6 signaling pathway in Ras mediated invasion and tumorigenesis.ResultsCellular migration, invasion, anchorage independent growth and tumorigenesis were largely abrogated in the Stat3-reduced cells compared to control cells. Analysis of MCF10A-Ras tumors revealed high levels of pStat3 and interleukin-6. Tumors derived from transgenic MMTV-K-Ras mice were also found to express pStat3 and IL-6. MCF10A-Ras cells, when grown in a three-dimensional Matrigel culture system revealed the appearance of the junctional protein E-Cadherin as a consequence of reducing Stat3 levels or inhibiting Stat3 activity. Decreasing IL-6 levels in the MCF10A-Ras cells abrogated tumorigenesis and reduced cell migration. By isolating Ras-expressing primary tumors and serially passaging these cells in two-dimensional culture led to a decrease in IL-6 and pStat3 levels with the reappearance of E-Cadherin.ConclusionsThe cellular and environmental context can lead to differential IL-6/pStat3 signaling and a dependency on this cytokine and transcription factor for migration, invasion and tumorigenesis.
| S-EPMC3096973 | biostudies-literature